5TK5

Crystal structure of human 3HAO with iron bound in the active site

5TK5 の概要

• エントリーDOI: 10.2210/pdb5tk5/pdb
• 分子名称: 3-hydroxyanthranilate 3,4-dioxygenase, FE (III) ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: 3-hydroxyanthranilate oxygenase dioxygenase, cupin kynurenine pathway, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33236.41

構造登録者

Pidugu, L.S.,Toth, E.A. (登録日: 2016-10-06, 公開日: 2017-04-12, 最終更新日: 2023-10-04)

主引用文献

Pidugu, L.S.,Neu, H.,Wong, T.L.,Pozharski, E.,Molloy, J.L.,Michel, S.L.,Toth, E.A.
Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site.
Acta Crystallogr D Struct Biol, 73:340-348, 2017

PubMed Abstract: 3-Hydroxyanthranilate 3,4-dioxygenase (3HAO) is an enzyme in the microglial branch of the kynurenine pathway of tryptophan degradation. 3HAO is a non-heme iron-containing, ring-cleaving extradiol dioxygenase that catalyzes the addition of both atoms of O to the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3-HANA) to form quinolinic acid (QUIN). QUIN is a highly potent excitotoxin that has been implicated in a number of neurodegenerative conditions, making 3HAO a target for pharmacological downregulation. Here, the first crystal structure of human 3HAO with the native iron bound in its active site is presented, together with an additional structure with zinc (a known inhibitor of human 3HAO) bound in the active site. The metal-binding environment is examined both structurally and via inductively coupled plasma mass spectrometry (ICP-MS), X-ray fluorescence spectroscopy (XRF) and electron paramagnetic resonance spectroscopy (EPR). The studies identified Met35 as the source of potential new interactions with substrates and inhibitors, which may prove useful in future therapeutic efforts.

PubMed: 28375145
DOI: 10.1107/S2059798317002029

実験手法

X-RAY DIFFRACTION (1.88 Å)